Wyndham H. Wilson, MD, PhD: Shedding Light on the Complexity of Lymphoma Through a Lifetime of Illuminating Research

During the clinical trials in the early 1990s, I was writing my own studies and virtually running them on my own. Fast forward to the present, and we are running multiple studies across all phases, which all have complicated translational components to them.

— Wyndham H. Wilson, MD, PhD

Dear Dr. Wilson: I am writing to express our family’s deepest and heartfelt appreciation for the lifesaving care you and your team provided for our son, Patrick…. I don’t know how widely it is known that you save lives at the National Cancer Institute—offering hope to people like Patrick, who have run out of options.”

So begins a letter addressed to Wyndham H. Wilson, MD, PhD, from a father whose son Dr. Wilson and his team had successfully treated for central nervous system lymphoma. Dr. Wilson, an internationally regarded expert on lymphomas, has spent the better part of his notable career at the National Cancer Institute (NCI). His life’s work has given the medical world a much clearer understanding of the complexity of lymphoma.

A Childhood Abroad

Dr. Wilson’s father was an academic surgeon who sought to bring high-value medicine to countries in the developing world. “I was born in San Francisco, but when I was about 1 year old, we relocated to Lebanon, and my father assumed a position at the American University of Beirut, where he was the dean of the medical school and head of the surgical department. I grew up on the university campus in Lebanon and remained there until the age of 17,” said Dr. Wilson, adding, “I had an interest in medicine, probably from the time I was 4 years old. I used to accompany my father as he made rounds in the laboratories and read everything I could that had to do with anatomy or science.”

Dr. Wilson attended an international school in Beirut called the American Community School, which provided education for children from kindergarten through 12th grade. “Back then there were a lot of kids whose parents were associated, in one way or another, with the diplomatic service or the oil industry in the Arab Gulf states. I’d say that about 80% of the students were American, as were most of the teachers. The rest of the teachers were predominantly from Europe, although there were a few Arabic teachers, too. I’d liken the quality of education to a good American preparatory school. The school is still fully operative to this day,” said Dr. Wilson.

Seeking Stability at Stanford

Having left the United States at such an early age, Dr. Wilson was spared the separation anxiety older children often suffer during a major move from home. “I actually felt uprooted at 17 years old when we left Lebanon, feeling like I’d been moved to a completely alien environment, which was the United States. We settled in Palo Alto, California, where my mother was originally from, and my father took a position as Professor of Surgery at Stanford University,” said Dr. Wilson, adding, “I finished up my last 2 years of high school at the Palo Alto High School and then applied for college.”

Asked to describe his college experience, Dr. Wilson said, “There was never much thought about where I was going to go, so I applied to one university: Stanford. I received a combined BA (human biology) and MS (biology) in 1975, and an MD and PhD (neurobiology) in 1981 from Stanford University. I then completed my internship and residency training at Stanford as well. I’d found the move from Lebanon back to the States very disruptive, which was one reason that I stayed at Stanford throughout my college and medical schooling, having no desire to move about. I liked the stability Stanford offered,” said Dr. Wilson.

Asked about his decision to pursue a career in oncology, Dr. Wilson said, “As a young boy I’d not only been interested in medicine, but I also had an interest in science. I went to school in the 1970s, finishing up in the early 1980s, a time when oncology was beginning to make significant strides in research and treatment. And for the first time, we were beginning to understand the molecular basis of cancer, so I became intrigued by the science behind oncology and the possibilities ahead both in the lab and the clinic.”

Mentors at the NCI

He continued, “At that time, Stanford was heavily into lymphoma research. In fact, early on in medical school, I’d applied to a number of oncology fellowships, focusing on the top lymphoma groups. Interestingly, I was turned down by Stanford but was accepted by the NCI, which turned out to be a career-defining move. I finished my residency at Stanford and went to the NCI in 1984.”

Dr. Wilson explained that, as in any fellowship program, the first year at the NCI was consumed by a lot of “drudge” work, but in the ensuing years he found the NCI to be an environment that encouraged fellows to engage in research, which was his primary focus.

“After doing the clinical part of the fellowship, I went on to do my research years, during which I had two terrific mentors, who helped my career path mature. First there was Dr. Dan Longo, and then some time later, Dr. Bruce Chabner. It was while working under these two great doctors that I truly developed my core instincts in how one should approach cancer research and the scientific methods for conducting studies, which have stayed with me to this day. Although I did my PhD in neurobiology, at the NCI, my work was focused on protein chemistry,” said Dr. Wilson.

The Importance of Solid Trial Design

“Even though I ultimately moved more toward the translational end of research with very deep roots with laboratories, I personally do not run a lab. I’m concerned with developing many of the concepts of design and hypotheses so that the trials can give us clear outcomes, whether positive or negative. I find that many of the clinical trials underway are not really thought through and are just empirically derived. In such, much of what we could learn from trials is simply lost,” said Dr. Wilson.

Dr. Wilson began his fellowship at the NCI in the “Golden Era” of groundbreaking discovery, a time of less paperwork and far fewer roadblocks on the road to cancer drug development. Asked to compare and contrast the 1970s with contemporary drug development, Dr. Wilson responded, “The challenges in the drug development process have become much greater. Interestingly, the core for what is necessary for institutional review board approval was actually developed in the 1980s and 1990s. But the approval process is essentially just guidelines, and how they are interpreted and implemented is really what has changed over the past few decades. Clearly, guidance has become more specific, but the core messages remain the same.”

“Unfortunately, much of the general language in the early guidelines has been, if you will, filled in. Although the safety regulations and integrity of the guidance have increased, the oversight needs and the amount of ancillary people needed to help weed through all of these regulatory issues have also increased enormously, such so that it has made the approval process very sluggish,” he said.

A Day in the Life

Dr. Wilson, who is currently the Head of NCI’s Lymphoma Therapeutics Section and a senior investigator, has been at the Institute for the majority of his career. He commented that when he first began the Lymphoma Therapeutics Section, it was basically a one-man show.

“During the clinical trials in the early 1990s, I was writing my own studies and virtually running them on my own. Fast forward to the present, and we are running multiple studies across all phases, which all have complicated translational components to them. I’ve amassed a staff of physicians, researchers, research nurses, and data managers to run these clinical trials. I provide oversight to the operations and intellectual foresight into the future. Moreover, there has become an increasing need for me to interact with industry at an earlier stage of a drug’s life cycle. The NCI provides a lot of the intellectual structural underpinning for trial development, and we work with industry,” explained Dr. Wilson. “I also work closely with Dr. Louis Staudt, one the world’s foremost lymphoma experts,” he added. In essence, he and I closely collaborate to translate his basic observations and conversely to provide translational endpoints for hypotheses that come from our clinical studies.”

When Dr. Wilson isn’t at the NCI running the lymphoma section, he’s usually in an airport. “I do a lot of traveling to lecture on our work at the NCI and serve on various committees, such as chairing the U.S. Food and Drug Administration Oncologic Drug Advisory Committee, which I completed several years ago. So I have a fairly full schedule,” said Dr. Wilson.

As a researcher who has seen an incredible arc of knowledge and discovery in oncology over the course of his esteemed career, have the modest gains in survival we’ve seen in some cancers dampened his outlook for the future? “Absolutely not. In fact I’m more optimistic now than ever,” Dr. Wilson maintained. “One very bright light has been the renewed interest in immune therapy. Although we’ve known that the immune system can help eradicate subclinical cancers, we’ve reached a point in which we feel we can harness the immune system, perhaps in conjunction with targeted biologics, and see major advances in curative therapies. Another thing that makes immunotherapy so exciting is that it is not pathway-specific. There is no reason for us in the oncology community to be anything but optimistic.” ■